{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T14:02:23Z","timestamp":1789221743856,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T00:00:00Z","timestamp":1578441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2020,4]]},"abstract":"Abstract<\/jats:title>\n \n Both\n JAK2<\/jats:italic>\n V617F and calreticulin (\n CALR)<\/jats:italic>\n mutated essential thrombocythemia (ET) patients have different clinical characteristics, with lower thrombosis risk in patients with\n CALR<\/jats:italic>\n mutations. To elucidate the mechanism for this lower risk we studied platelet function in ET patients with either\n JAK2<\/jats:italic>\n V617F or a\n CALR<\/jats:italic>\n mutation. Platelet activation state was similar in ET and healthy controls at baseline using P\u2010selectin and PAC1 flow cytometry analysis. However,\n CALR<\/jats:italic>\n mutated platelets were significantly less activated following ADP stimulation, compared to control or\n JAK2<\/jats:italic>\n mutated platelets (\n P<\/jats:italic>\n <\u2009.001). In live\u2010cell imaging of platelet attachment to immobilized fibrinogen by Interference Reflection Microscopy (IRM), the number of attached\n CALR<\/jats:italic>\n mutated platelets was lower compared to control and\n JAK2<\/jats:italic>\n mutated platelets, with lower fractions of platelets achieving the fully spread state (90%, 78% and 54% of adherent cells for control,\n JAK2<\/jats:italic>\n and\n CALR<\/jats:italic>\n mutated subjects, respectively). Compared to controls, ET patients, regardless of the mutation type, had increased numbers of immature platelets (IP) and leukocyte platelet aggregates (LPA), as well as plasma sP\u2010selectin. These were all correlated with the platelet count and not to the state of platelet activation. We also found that intracellular free Ca\n 2+<\/jats:sup>\n was increased in resting ET compared to control platelets. Note, CALR had a more dispersed localization in activated ET platelets compared to healthy controls, and mutated CALR interact physically with TpoR in\n CALR<\/jats:italic>\n mutated platelets. We hypothesize that defects in platelet activation and spreading in\n CALR<\/jats:italic>\n mutated patients can explain, at least in part, the lower thrombotic tendency in\n CALR<\/jats:italic>\n mutated ET patients.\n <\/jats:p>","DOI":"10.1002\/ajh.25713","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T07:14:32Z","timestamp":1577085272000},"page":"379-386","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Platelets from Calreticulin mutated essential thrombocythemia patients are less reactive than JAK2 V617F mutated platelets"],"prefix":"10.1002","volume":"95","author":[{"given":"Hagit","family":"Hauschner","sequence":"first","affiliation":[{"name":"Scientific Equipment Center, The Mina & Everard Goodman Faculty of Life Sciences Bar\u2010Ilan University Ramat\u2010Gan Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Bokstad Horev","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology The Weizmann Institute of Science Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Modi","family":"Misgav","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine Tel Aviv University Tel\u2010Aviv Israel"},{"name":"The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center Tel Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meital","family":"Nagar","sequence":"additional","affiliation":[{"name":"Molecular Hematology Laboratory Sheba Medical Center Tel Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri","family":"Seligsohn","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine Tel Aviv University Tel\u2010Aviv Israel"},{"name":"The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center Tel Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurit","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine Tel Aviv University Tel\u2010Aviv Israel"},{"name":"The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center Tel Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-328X","authenticated-orcid":false,"given":"Maya","family":"Koren\u2010Michowitz","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine Tel Aviv University Tel\u2010Aviv Israel"},{"name":"Department of Hematology Shamir Medical Center (Assaf Harofeh) Zerifin Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,8]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25303"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00963"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-019315"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-671172"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-3777"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-538983"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2015.94"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(16)30102-5"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.12051"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.09021.x"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cptx.46"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH09-09-0663"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05032.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2007.01.053"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(16)30159-1"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(16)30152-9"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21338"},{"issue":"2","key":"e_1_2_5_19_1","first-page":"169","article-title":"Increased 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